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Schyman P, Printz RL, Pannala VR, et al. Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat. Toxicol Appl Pharmacol. 2021;430:115713doi: 10.1016/j.taap.2021.115713.
Schyman, P., Printz, R. L., Pannala, V. R., AbdulHameed, M. D. M., Estes, S. K., Shiota, C., Boyd, K. L., Shiota, M., & Wallqvist, A. (2021). Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat. Toxicology and applied pharmacology, 430115713. https://doi.org/10.1016/j.taap.2021.115713
Schyman, Patric, et al. "Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat." Toxicology and applied pharmacology vol. 430 (2021): 115713. doi: https://doi.org/10.1016/j.taap.2021.115713
Schyman P, Printz RL, Pannala VR, AbdulHameed MDM, Estes SK, Shiota C, Boyd KL, Shiota M, Wallqvist A. Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat. Toxicol Appl Pharmacol. 2021 Nov 01;430:115713. doi: 10.1016/j.taap.2021.115713. Epub 2021 Sep 04. PMID: 34492290; PMCID: PMC8511347.
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Toxicol Appl Pharmacol. 2021 Nov 01;430:115713. doi: 10.1016/j.taap.2021.115713. Epub 2021 Sep 04.

Genomics and metabolomics of early-stage thioacetamide-induced liver injury: An interspecies study between guinea pig and rat.

Toxicology and applied pharmacology

Patric Schyman, Richard L Printz, Venkat R Pannala, Mohamed Diwan M AbdulHameed, Shanea K Estes, Chiyo Shiota, Kelli Lynn Boyd, Masakazu Shiota, Anders Wallqvist

Affiliations

  1. Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
  2. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
  3. Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA. Electronic address: [email protected].
  4. Department of Pathology, Microbiology and Immunology, Division of Comparative Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  5. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: [email protected].
  6. Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, USA. Electronic address: [email protected].

PMID: 34492290 PMCID: PMC8511347 DOI: 10.1016/j.taap.2021.115713

Abstract

To study the complex processes involved in liver injuries, researchers rely on animal investigations, using chemically or surgically induced liver injuries, to extrapolate findings and infer human health risks. However, this presents obvious challenges in performing a detailed comparison and validation between the highly controlled animal models and development of liver injuries in humans. Furthermore, it is not clear whether there are species-dependent and -independent molecular initiating events or processes that cause liver injury before they eventually lead to end-stage liver disease. Here, we present a side-by-side study of rats and guinea pigs using thioacetamide to examine the similarities between early molecular initiating events during an acute-phase liver injury. We exposed Sprague Dawley rats and Hartley guinea pigs to a single dose of 25 or 100 mg/kg thioacetamide and collected blood plasma for metabolomic analysis and liver tissue for RNA-sequencing. The subsequent toxicogenomic analysis identified consistent liver injury trends in both genomic and metabolomic data within 24 and 33 h after thioacetamide exposure in rats and guinea pigs, respectively. In particular, we found species similarities in the key injury phenotypes of inflammation and fibrogenesis in our gene module analysis for liver injury phenotypes. We identified expression of several common genes (e.g., SPP1, TNSF18, SERPINE1, CLDN4, TIMP1, CD44, and LGALS3), activation of injury-specific KEGG pathways, and alteration of plasma metabolites involved in amino acid and bile acid metabolism as some of the key molecular processes that changed early upon thioacetamide exposure and could play a major role in the initiation of acute liver injury.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Biomarkers; Gene expression; Interspecies translation; Liver injury; Metabolomics

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